Infectious Complications Predict Premature $ CD8^{+} $ T-cell Senescence in CD40 Ligand-Deficient Patients
Purpose CD40 ligand (CD40L)-deficient patients display increased susceptibilities to infections that can be mitigated with effective prophylactic strategies including immunoglobulin G (IgG) replacement and prophylactic antibiotics. $ CD8^{+} $ T-cell senescence has been described in CD40L deficiency...
Ausführliche Beschreibung
Autor*in: |
Shin, Junghee J. [verfasserIn] Catanzaro, Jason [verfasserIn] Yonkof, Jennifer R. [verfasserIn] Delmonte, Ottavia [verfasserIn] Sacco, Keith [verfasserIn] Shin, Min Sun [verfasserIn] Reddy, Srikar [verfasserIn] Whittington, Paula J. [verfasserIn] Soffer, Gary [verfasserIn] Mustillo, Peter J. [verfasserIn] Sullivan, Kathleen E. [verfasserIn] Notarangelo, Luigi D. [verfasserIn] Abraham, Roshini S. [verfasserIn] Romberg, Neil [verfasserIn] Kang, Insoo [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2021 |
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Schlagwörter: |
X-linked CD40 ligand deficiency class switching recombination defect |
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Übergeordnetes Werk: |
Enthalten in: Journal of clinical immunology - Dordrecht [u.a.] : Springer Science + Business Media B.V, 1981, 41(2021), 4 vom: 26. Jan., Seite 795-806 |
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Übergeordnetes Werk: |
volume:41 ; year:2021 ; number:4 ; day:26 ; month:01 ; pages:795-806 |
Links: |
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DOI / URN: |
10.1007/s10875-021-00968-x |
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Katalog-ID: |
SPR043858724 |
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100 | 1 | |a Shin, Junghee J. |e verfasserin |4 aut | |
245 | 1 | 0 | |a Infectious Complications Predict Premature $ CD8^{+} $ T-cell Senescence in CD40 Ligand-Deficient Patients |
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520 | |a Purpose CD40 ligand (CD40L)-deficient patients display increased susceptibilities to infections that can be mitigated with effective prophylactic strategies including immunoglobulin G (IgG) replacement and prophylactic antibiotics. $ CD8^{+} $ T-cell senescence has been described in CD40L deficiency, but it is unclear if this is an intrinsic feature of the disease or secondary to infectious exposures. To address this question, we assessed $ CD8^{+} $ T-cell senescence and its relationship to clinical histories, including prophylaxis adherence and infections, in CD40L-deficient patients. Methods Peripheral $ CD8^{+} $ T-cells from seven CD40L-deficient patients and healthy controls (HCs) were assessed for senescent features using T-cell receptor excision circle (TREC) analysis, flow cytometry, cytometry by time of flight (CyTOF) and in vitro functional determinations including CMV-specific proliferation and cytokine release assays. Results Three patients (5, 28, and 34 years old) who were poorly adherent to immunoglobulin G replacement and Pneumocystis jirovecii pneumonia (PJP) prophylaxis and/or experienced multiple childhood pneumonias (patient group 1) had an expansion of effector memory $ CD8^{+} $ T-cells with the senescent phenotype when compared to HCs. Such changes were not observed in the patient group 2 (four patients, 16, 22, 24, and 33 years old) who were life-long adherents to prophylaxis and experienced few infectious complications. CyTOF analysis of $ CD8^{+} $ T-cells from the 5-year-old patient and older adult HCs showed similar expression patterns of senescence-associated molecules. Conclusions Our findings support that recurrent infections and non-adherence to prophylaxis promote early $ CD8^{+} $ T-cell senescence in CD40L deficiency. Premature senescence may increase malignant susceptibilities and further exacerbate infectious risk in CD40L-deficient patients. | ||
650 | 4 | |a X-linked CD40 ligand deficiency |7 (dpeaa)DE-He213 | |
650 | 4 | |a CD8 |7 (dpeaa)DE-He213 | |
650 | 4 | |a T-cell senescence |7 (dpeaa)DE-He213 | |
650 | 4 | |a combined immunodeficiency |7 (dpeaa)DE-He213 | |
650 | 4 | |a class switching recombination defect |7 (dpeaa)DE-He213 | |
650 | 4 | |a immunoglobulin replacement therapy |7 (dpeaa)DE-He213 | |
650 | 4 | |a pneumonia (PJP) prophylactic antibiotics |7 (dpeaa)DE-He213 | |
700 | 1 | |a Catanzaro, Jason |e verfasserin |4 aut | |
700 | 1 | |a Yonkof, Jennifer R. |e verfasserin |4 aut | |
700 | 1 | |a Delmonte, Ottavia |e verfasserin |4 aut | |
700 | 1 | |a Sacco, Keith |e verfasserin |4 aut | |
700 | 1 | |a Shin, Min Sun |e verfasserin |4 aut | |
700 | 1 | |a Reddy, Srikar |e verfasserin |4 aut | |
700 | 1 | |a Whittington, Paula J. |e verfasserin |4 aut | |
700 | 1 | |a Soffer, Gary |e verfasserin |4 aut | |
700 | 1 | |a Mustillo, Peter J. |e verfasserin |4 aut | |
700 | 1 | |a Sullivan, Kathleen E. |e verfasserin |4 aut | |
700 | 1 | |a Notarangelo, Luigi D. |e verfasserin |4 aut | |
700 | 1 | |a Abraham, Roshini S. |e verfasserin |4 aut | |
700 | 1 | |a Romberg, Neil |e verfasserin |4 aut | |
700 | 1 | |a Kang, Insoo |e verfasserin |4 aut | |
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10.1007/s10875-021-00968-x doi (DE-627)SPR043858724 (DE-599)SPRs10875-021-00968-x-e (SPR)s10875-021-00968-x-e DE-627 ger DE-627 rakwb eng 610 ASE 44.45 bkl Shin, Junghee J. verfasserin aut Infectious Complications Predict Premature $ CD8^{+} $ T-cell Senescence in CD40 Ligand-Deficient Patients 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose CD40 ligand (CD40L)-deficient patients display increased susceptibilities to infections that can be mitigated with effective prophylactic strategies including immunoglobulin G (IgG) replacement and prophylactic antibiotics. $ CD8^{+} $ T-cell senescence has been described in CD40L deficiency, but it is unclear if this is an intrinsic feature of the disease or secondary to infectious exposures. To address this question, we assessed $ CD8^{+} $ T-cell senescence and its relationship to clinical histories, including prophylaxis adherence and infections, in CD40L-deficient patients. Methods Peripheral $ CD8^{+} $ T-cells from seven CD40L-deficient patients and healthy controls (HCs) were assessed for senescent features using T-cell receptor excision circle (TREC) analysis, flow cytometry, cytometry by time of flight (CyTOF) and in vitro functional determinations including CMV-specific proliferation and cytokine release assays. Results Three patients (5, 28, and 34 years old) who were poorly adherent to immunoglobulin G replacement and Pneumocystis jirovecii pneumonia (PJP) prophylaxis and/or experienced multiple childhood pneumonias (patient group 1) had an expansion of effector memory $ CD8^{+} $ T-cells with the senescent phenotype when compared to HCs. Such changes were not observed in the patient group 2 (four patients, 16, 22, 24, and 33 years old) who were life-long adherents to prophylaxis and experienced few infectious complications. CyTOF analysis of $ CD8^{+} $ T-cells from the 5-year-old patient and older adult HCs showed similar expression patterns of senescence-associated molecules. Conclusions Our findings support that recurrent infections and non-adherence to prophylaxis promote early $ CD8^{+} $ T-cell senescence in CD40L deficiency. Premature senescence may increase malignant susceptibilities and further exacerbate infectious risk in CD40L-deficient patients. X-linked CD40 ligand deficiency (dpeaa)DE-He213 CD8 (dpeaa)DE-He213 T-cell senescence (dpeaa)DE-He213 combined immunodeficiency (dpeaa)DE-He213 class switching recombination defect (dpeaa)DE-He213 immunoglobulin replacement therapy (dpeaa)DE-He213 pneumonia (PJP) prophylactic antibiotics (dpeaa)DE-He213 Catanzaro, Jason verfasserin aut Yonkof, Jennifer R. verfasserin aut Delmonte, Ottavia verfasserin aut Sacco, Keith verfasserin aut Shin, Min Sun verfasserin aut Reddy, Srikar verfasserin aut Whittington, Paula J. verfasserin aut Soffer, Gary verfasserin aut Mustillo, Peter J. verfasserin aut Sullivan, Kathleen E. verfasserin aut Notarangelo, Luigi D. verfasserin aut Abraham, Roshini S. verfasserin aut Romberg, Neil verfasserin aut Kang, Insoo verfasserin aut Enthalten in Journal of clinical immunology Dordrecht [u.a.] : Springer Science + Business Media B.V, 1981 41(2021), 4 vom: 26. Jan., Seite 795-806 (DE-627)320573362 (DE-600)2016755-6 1573-2592 nnns volume:41 year:2021 number:4 day:26 month:01 pages:795-806 https://dx.doi.org/10.1007/s10875-021-00968-x lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.45 ASE AR 41 2021 4 26 01 795-806 |
spelling |
10.1007/s10875-021-00968-x doi (DE-627)SPR043858724 (DE-599)SPRs10875-021-00968-x-e (SPR)s10875-021-00968-x-e DE-627 ger DE-627 rakwb eng 610 ASE 44.45 bkl Shin, Junghee J. verfasserin aut Infectious Complications Predict Premature $ CD8^{+} $ T-cell Senescence in CD40 Ligand-Deficient Patients 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose CD40 ligand (CD40L)-deficient patients display increased susceptibilities to infections that can be mitigated with effective prophylactic strategies including immunoglobulin G (IgG) replacement and prophylactic antibiotics. $ CD8^{+} $ T-cell senescence has been described in CD40L deficiency, but it is unclear if this is an intrinsic feature of the disease or secondary to infectious exposures. To address this question, we assessed $ CD8^{+} $ T-cell senescence and its relationship to clinical histories, including prophylaxis adherence and infections, in CD40L-deficient patients. Methods Peripheral $ CD8^{+} $ T-cells from seven CD40L-deficient patients and healthy controls (HCs) were assessed for senescent features using T-cell receptor excision circle (TREC) analysis, flow cytometry, cytometry by time of flight (CyTOF) and in vitro functional determinations including CMV-specific proliferation and cytokine release assays. Results Three patients (5, 28, and 34 years old) who were poorly adherent to immunoglobulin G replacement and Pneumocystis jirovecii pneumonia (PJP) prophylaxis and/or experienced multiple childhood pneumonias (patient group 1) had an expansion of effector memory $ CD8^{+} $ T-cells with the senescent phenotype when compared to HCs. Such changes were not observed in the patient group 2 (four patients, 16, 22, 24, and 33 years old) who were life-long adherents to prophylaxis and experienced few infectious complications. CyTOF analysis of $ CD8^{+} $ T-cells from the 5-year-old patient and older adult HCs showed similar expression patterns of senescence-associated molecules. Conclusions Our findings support that recurrent infections and non-adherence to prophylaxis promote early $ CD8^{+} $ T-cell senescence in CD40L deficiency. Premature senescence may increase malignant susceptibilities and further exacerbate infectious risk in CD40L-deficient patients. X-linked CD40 ligand deficiency (dpeaa)DE-He213 CD8 (dpeaa)DE-He213 T-cell senescence (dpeaa)DE-He213 combined immunodeficiency (dpeaa)DE-He213 class switching recombination defect (dpeaa)DE-He213 immunoglobulin replacement therapy (dpeaa)DE-He213 pneumonia (PJP) prophylactic antibiotics (dpeaa)DE-He213 Catanzaro, Jason verfasserin aut Yonkof, Jennifer R. verfasserin aut Delmonte, Ottavia verfasserin aut Sacco, Keith verfasserin aut Shin, Min Sun verfasserin aut Reddy, Srikar verfasserin aut Whittington, Paula J. verfasserin aut Soffer, Gary verfasserin aut Mustillo, Peter J. verfasserin aut Sullivan, Kathleen E. verfasserin aut Notarangelo, Luigi D. verfasserin aut Abraham, Roshini S. verfasserin aut Romberg, Neil verfasserin aut Kang, Insoo verfasserin aut Enthalten in Journal of clinical immunology Dordrecht [u.a.] : Springer Science + Business Media B.V, 1981 41(2021), 4 vom: 26. Jan., Seite 795-806 (DE-627)320573362 (DE-600)2016755-6 1573-2592 nnns volume:41 year:2021 number:4 day:26 month:01 pages:795-806 https://dx.doi.org/10.1007/s10875-021-00968-x lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.45 ASE AR 41 2021 4 26 01 795-806 |
allfields_unstemmed |
10.1007/s10875-021-00968-x doi (DE-627)SPR043858724 (DE-599)SPRs10875-021-00968-x-e (SPR)s10875-021-00968-x-e DE-627 ger DE-627 rakwb eng 610 ASE 44.45 bkl Shin, Junghee J. verfasserin aut Infectious Complications Predict Premature $ CD8^{+} $ T-cell Senescence in CD40 Ligand-Deficient Patients 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose CD40 ligand (CD40L)-deficient patients display increased susceptibilities to infections that can be mitigated with effective prophylactic strategies including immunoglobulin G (IgG) replacement and prophylactic antibiotics. $ CD8^{+} $ T-cell senescence has been described in CD40L deficiency, but it is unclear if this is an intrinsic feature of the disease or secondary to infectious exposures. To address this question, we assessed $ CD8^{+} $ T-cell senescence and its relationship to clinical histories, including prophylaxis adherence and infections, in CD40L-deficient patients. Methods Peripheral $ CD8^{+} $ T-cells from seven CD40L-deficient patients and healthy controls (HCs) were assessed for senescent features using T-cell receptor excision circle (TREC) analysis, flow cytometry, cytometry by time of flight (CyTOF) and in vitro functional determinations including CMV-specific proliferation and cytokine release assays. Results Three patients (5, 28, and 34 years old) who were poorly adherent to immunoglobulin G replacement and Pneumocystis jirovecii pneumonia (PJP) prophylaxis and/or experienced multiple childhood pneumonias (patient group 1) had an expansion of effector memory $ CD8^{+} $ T-cells with the senescent phenotype when compared to HCs. Such changes were not observed in the patient group 2 (four patients, 16, 22, 24, and 33 years old) who were life-long adherents to prophylaxis and experienced few infectious complications. CyTOF analysis of $ CD8^{+} $ T-cells from the 5-year-old patient and older adult HCs showed similar expression patterns of senescence-associated molecules. Conclusions Our findings support that recurrent infections and non-adherence to prophylaxis promote early $ CD8^{+} $ T-cell senescence in CD40L deficiency. Premature senescence may increase malignant susceptibilities and further exacerbate infectious risk in CD40L-deficient patients. X-linked CD40 ligand deficiency (dpeaa)DE-He213 CD8 (dpeaa)DE-He213 T-cell senescence (dpeaa)DE-He213 combined immunodeficiency (dpeaa)DE-He213 class switching recombination defect (dpeaa)DE-He213 immunoglobulin replacement therapy (dpeaa)DE-He213 pneumonia (PJP) prophylactic antibiotics (dpeaa)DE-He213 Catanzaro, Jason verfasserin aut Yonkof, Jennifer R. verfasserin aut Delmonte, Ottavia verfasserin aut Sacco, Keith verfasserin aut Shin, Min Sun verfasserin aut Reddy, Srikar verfasserin aut Whittington, Paula J. verfasserin aut Soffer, Gary verfasserin aut Mustillo, Peter J. verfasserin aut Sullivan, Kathleen E. verfasserin aut Notarangelo, Luigi D. verfasserin aut Abraham, Roshini S. verfasserin aut Romberg, Neil verfasserin aut Kang, Insoo verfasserin aut Enthalten in Journal of clinical immunology Dordrecht [u.a.] : Springer Science + Business Media B.V, 1981 41(2021), 4 vom: 26. Jan., Seite 795-806 (DE-627)320573362 (DE-600)2016755-6 1573-2592 nnns volume:41 year:2021 number:4 day:26 month:01 pages:795-806 https://dx.doi.org/10.1007/s10875-021-00968-x lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.45 ASE AR 41 2021 4 26 01 795-806 |
allfieldsGer |
10.1007/s10875-021-00968-x doi (DE-627)SPR043858724 (DE-599)SPRs10875-021-00968-x-e (SPR)s10875-021-00968-x-e DE-627 ger DE-627 rakwb eng 610 ASE 44.45 bkl Shin, Junghee J. verfasserin aut Infectious Complications Predict Premature $ CD8^{+} $ T-cell Senescence in CD40 Ligand-Deficient Patients 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose CD40 ligand (CD40L)-deficient patients display increased susceptibilities to infections that can be mitigated with effective prophylactic strategies including immunoglobulin G (IgG) replacement and prophylactic antibiotics. $ CD8^{+} $ T-cell senescence has been described in CD40L deficiency, but it is unclear if this is an intrinsic feature of the disease or secondary to infectious exposures. To address this question, we assessed $ CD8^{+} $ T-cell senescence and its relationship to clinical histories, including prophylaxis adherence and infections, in CD40L-deficient patients. Methods Peripheral $ CD8^{+} $ T-cells from seven CD40L-deficient patients and healthy controls (HCs) were assessed for senescent features using T-cell receptor excision circle (TREC) analysis, flow cytometry, cytometry by time of flight (CyTOF) and in vitro functional determinations including CMV-specific proliferation and cytokine release assays. Results Three patients (5, 28, and 34 years old) who were poorly adherent to immunoglobulin G replacement and Pneumocystis jirovecii pneumonia (PJP) prophylaxis and/or experienced multiple childhood pneumonias (patient group 1) had an expansion of effector memory $ CD8^{+} $ T-cells with the senescent phenotype when compared to HCs. Such changes were not observed in the patient group 2 (four patients, 16, 22, 24, and 33 years old) who were life-long adherents to prophylaxis and experienced few infectious complications. CyTOF analysis of $ CD8^{+} $ T-cells from the 5-year-old patient and older adult HCs showed similar expression patterns of senescence-associated molecules. Conclusions Our findings support that recurrent infections and non-adherence to prophylaxis promote early $ CD8^{+} $ T-cell senescence in CD40L deficiency. Premature senescence may increase malignant susceptibilities and further exacerbate infectious risk in CD40L-deficient patients. X-linked CD40 ligand deficiency (dpeaa)DE-He213 CD8 (dpeaa)DE-He213 T-cell senescence (dpeaa)DE-He213 combined immunodeficiency (dpeaa)DE-He213 class switching recombination defect (dpeaa)DE-He213 immunoglobulin replacement therapy (dpeaa)DE-He213 pneumonia (PJP) prophylactic antibiotics (dpeaa)DE-He213 Catanzaro, Jason verfasserin aut Yonkof, Jennifer R. verfasserin aut Delmonte, Ottavia verfasserin aut Sacco, Keith verfasserin aut Shin, Min Sun verfasserin aut Reddy, Srikar verfasserin aut Whittington, Paula J. verfasserin aut Soffer, Gary verfasserin aut Mustillo, Peter J. verfasserin aut Sullivan, Kathleen E. verfasserin aut Notarangelo, Luigi D. verfasserin aut Abraham, Roshini S. verfasserin aut Romberg, Neil verfasserin aut Kang, Insoo verfasserin aut Enthalten in Journal of clinical immunology Dordrecht [u.a.] : Springer Science + Business Media B.V, 1981 41(2021), 4 vom: 26. Jan., Seite 795-806 (DE-627)320573362 (DE-600)2016755-6 1573-2592 nnns volume:41 year:2021 number:4 day:26 month:01 pages:795-806 https://dx.doi.org/10.1007/s10875-021-00968-x lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.45 ASE AR 41 2021 4 26 01 795-806 |
allfieldsSound |
10.1007/s10875-021-00968-x doi (DE-627)SPR043858724 (DE-599)SPRs10875-021-00968-x-e (SPR)s10875-021-00968-x-e DE-627 ger DE-627 rakwb eng 610 ASE 44.45 bkl Shin, Junghee J. verfasserin aut Infectious Complications Predict Premature $ CD8^{+} $ T-cell Senescence in CD40 Ligand-Deficient Patients 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose CD40 ligand (CD40L)-deficient patients display increased susceptibilities to infections that can be mitigated with effective prophylactic strategies including immunoglobulin G (IgG) replacement and prophylactic antibiotics. $ CD8^{+} $ T-cell senescence has been described in CD40L deficiency, but it is unclear if this is an intrinsic feature of the disease or secondary to infectious exposures. To address this question, we assessed $ CD8^{+} $ T-cell senescence and its relationship to clinical histories, including prophylaxis adherence and infections, in CD40L-deficient patients. Methods Peripheral $ CD8^{+} $ T-cells from seven CD40L-deficient patients and healthy controls (HCs) were assessed for senescent features using T-cell receptor excision circle (TREC) analysis, flow cytometry, cytometry by time of flight (CyTOF) and in vitro functional determinations including CMV-specific proliferation and cytokine release assays. Results Three patients (5, 28, and 34 years old) who were poorly adherent to immunoglobulin G replacement and Pneumocystis jirovecii pneumonia (PJP) prophylaxis and/or experienced multiple childhood pneumonias (patient group 1) had an expansion of effector memory $ CD8^{+} $ T-cells with the senescent phenotype when compared to HCs. Such changes were not observed in the patient group 2 (four patients, 16, 22, 24, and 33 years old) who were life-long adherents to prophylaxis and experienced few infectious complications. CyTOF analysis of $ CD8^{+} $ T-cells from the 5-year-old patient and older adult HCs showed similar expression patterns of senescence-associated molecules. Conclusions Our findings support that recurrent infections and non-adherence to prophylaxis promote early $ CD8^{+} $ T-cell senescence in CD40L deficiency. Premature senescence may increase malignant susceptibilities and further exacerbate infectious risk in CD40L-deficient patients. X-linked CD40 ligand deficiency (dpeaa)DE-He213 CD8 (dpeaa)DE-He213 T-cell senescence (dpeaa)DE-He213 combined immunodeficiency (dpeaa)DE-He213 class switching recombination defect (dpeaa)DE-He213 immunoglobulin replacement therapy (dpeaa)DE-He213 pneumonia (PJP) prophylactic antibiotics (dpeaa)DE-He213 Catanzaro, Jason verfasserin aut Yonkof, Jennifer R. verfasserin aut Delmonte, Ottavia verfasserin aut Sacco, Keith verfasserin aut Shin, Min Sun verfasserin aut Reddy, Srikar verfasserin aut Whittington, Paula J. verfasserin aut Soffer, Gary verfasserin aut Mustillo, Peter J. verfasserin aut Sullivan, Kathleen E. verfasserin aut Notarangelo, Luigi D. verfasserin aut Abraham, Roshini S. verfasserin aut Romberg, Neil verfasserin aut Kang, Insoo verfasserin aut Enthalten in Journal of clinical immunology Dordrecht [u.a.] : Springer Science + Business Media B.V, 1981 41(2021), 4 vom: 26. Jan., Seite 795-806 (DE-627)320573362 (DE-600)2016755-6 1573-2592 nnns volume:41 year:2021 number:4 day:26 month:01 pages:795-806 https://dx.doi.org/10.1007/s10875-021-00968-x lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.45 ASE AR 41 2021 4 26 01 795-806 |
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Enthalten in Journal of clinical immunology 41(2021), 4 vom: 26. Jan., Seite 795-806 volume:41 year:2021 number:4 day:26 month:01 pages:795-806 |
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X-linked CD40 ligand deficiency CD8 T-cell senescence combined immunodeficiency class switching recombination defect immunoglobulin replacement therapy pneumonia (PJP) prophylactic antibiotics |
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Shin, Junghee J. @@aut@@ Catanzaro, Jason @@aut@@ Yonkof, Jennifer R. @@aut@@ Delmonte, Ottavia @@aut@@ Sacco, Keith @@aut@@ Shin, Min Sun @@aut@@ Reddy, Srikar @@aut@@ Whittington, Paula J. @@aut@@ Soffer, Gary @@aut@@ Mustillo, Peter J. @@aut@@ Sullivan, Kathleen E. @@aut@@ Notarangelo, Luigi D. @@aut@@ Abraham, Roshini S. @@aut@@ Romberg, Neil @@aut@@ Kang, Insoo @@aut@@ |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR043858724</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519232918.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">210425s2021 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1007/s10875-021-00968-x</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR043858724</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)SPRs10875-021-00968-x-e</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s10875-021-00968-x-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">ASE</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">44.45</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Shin, Junghee J.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Infectious Complications Predict Premature $ CD8^{+} $ T-cell Senescence in CD40 Ligand-Deficient Patients</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2021</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Purpose CD40 ligand (CD40L)-deficient patients display increased susceptibilities to infections that can be mitigated with effective prophylactic strategies including immunoglobulin G (IgG) replacement and prophylactic antibiotics. $ CD8^{+} $ T-cell senescence has been described in CD40L deficiency, but it is unclear if this is an intrinsic feature of the disease or secondary to infectious exposures. To address this question, we assessed $ CD8^{+} $ T-cell senescence and its relationship to clinical histories, including prophylaxis adherence and infections, in CD40L-deficient patients. Methods Peripheral $ CD8^{+} $ T-cells from seven CD40L-deficient patients and healthy controls (HCs) were assessed for senescent features using T-cell receptor excision circle (TREC) analysis, flow cytometry, cytometry by time of flight (CyTOF) and in vitro functional determinations including CMV-specific proliferation and cytokine release assays. Results Three patients (5, 28, and 34 years old) who were poorly adherent to immunoglobulin G replacement and Pneumocystis jirovecii pneumonia (PJP) prophylaxis and/or experienced multiple childhood pneumonias (patient group 1) had an expansion of effector memory $ CD8^{+} $ T-cells with the senescent phenotype when compared to HCs. Such changes were not observed in the patient group 2 (four patients, 16, 22, 24, and 33 years old) who were life-long adherents to prophylaxis and experienced few infectious complications. CyTOF analysis of $ CD8^{+} $ T-cells from the 5-year-old patient and older adult HCs showed similar expression patterns of senescence-associated molecules. Conclusions Our findings support that recurrent infections and non-adherence to prophylaxis promote early $ CD8^{+} $ T-cell senescence in CD40L deficiency. 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|
author |
Shin, Junghee J. |
spellingShingle |
Shin, Junghee J. ddc 610 bkl 44.45 misc X-linked CD40 ligand deficiency misc CD8 misc T-cell senescence misc combined immunodeficiency misc class switching recombination defect misc immunoglobulin replacement therapy misc pneumonia (PJP) prophylactic antibiotics Infectious Complications Predict Premature $ CD8^{+} $ T-cell Senescence in CD40 Ligand-Deficient Patients |
authorStr |
Shin, Junghee J. |
ppnlink_with_tag_str_mv |
@@773@@(DE-627)320573362 |
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electronic Article |
dewey-ones |
610 - Medicine & health |
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keep |
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springer |
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true |
illustrated |
Not Illustrated |
issn |
1573-2592 |
topic_title |
610 ASE 44.45 bkl Infectious Complications Predict Premature $ CD8^{+} $ T-cell Senescence in CD40 Ligand-Deficient Patients X-linked CD40 ligand deficiency (dpeaa)DE-He213 CD8 (dpeaa)DE-He213 T-cell senescence (dpeaa)DE-He213 combined immunodeficiency (dpeaa)DE-He213 class switching recombination defect (dpeaa)DE-He213 immunoglobulin replacement therapy (dpeaa)DE-He213 pneumonia (PJP) prophylactic antibiotics (dpeaa)DE-He213 |
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ddc 610 bkl 44.45 misc X-linked CD40 ligand deficiency misc CD8 misc T-cell senescence misc combined immunodeficiency misc class switching recombination defect misc immunoglobulin replacement therapy misc pneumonia (PJP) prophylactic antibiotics |
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ddc 610 bkl 44.45 misc X-linked CD40 ligand deficiency misc CD8 misc T-cell senescence misc combined immunodeficiency misc class switching recombination defect misc immunoglobulin replacement therapy misc pneumonia (PJP) prophylactic antibiotics |
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ddc 610 bkl 44.45 misc X-linked CD40 ligand deficiency misc CD8 misc T-cell senescence misc combined immunodeficiency misc class switching recombination defect misc immunoglobulin replacement therapy misc pneumonia (PJP) prophylactic antibiotics |
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Infectious Complications Predict Premature $ CD8^{+} $ T-cell Senescence in CD40 Ligand-Deficient Patients |
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Infectious Complications Predict Premature $ CD8^{+} $ T-cell Senescence in CD40 Ligand-Deficient Patients |
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Shin, Junghee J. |
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Shin, Junghee J. Catanzaro, Jason Yonkof, Jennifer R. Delmonte, Ottavia Sacco, Keith Shin, Min Sun Reddy, Srikar Whittington, Paula J. Soffer, Gary Mustillo, Peter J. Sullivan, Kathleen E. Notarangelo, Luigi D. Abraham, Roshini S. Romberg, Neil Kang, Insoo |
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infectious complications predict premature $ cd8^{+} $ t-cell senescence in cd40 ligand-deficient patients |
title_auth |
Infectious Complications Predict Premature $ CD8^{+} $ T-cell Senescence in CD40 Ligand-Deficient Patients |
abstract |
Purpose CD40 ligand (CD40L)-deficient patients display increased susceptibilities to infections that can be mitigated with effective prophylactic strategies including immunoglobulin G (IgG) replacement and prophylactic antibiotics. $ CD8^{+} $ T-cell senescence has been described in CD40L deficiency, but it is unclear if this is an intrinsic feature of the disease or secondary to infectious exposures. To address this question, we assessed $ CD8^{+} $ T-cell senescence and its relationship to clinical histories, including prophylaxis adherence and infections, in CD40L-deficient patients. Methods Peripheral $ CD8^{+} $ T-cells from seven CD40L-deficient patients and healthy controls (HCs) were assessed for senescent features using T-cell receptor excision circle (TREC) analysis, flow cytometry, cytometry by time of flight (CyTOF) and in vitro functional determinations including CMV-specific proliferation and cytokine release assays. Results Three patients (5, 28, and 34 years old) who were poorly adherent to immunoglobulin G replacement and Pneumocystis jirovecii pneumonia (PJP) prophylaxis and/or experienced multiple childhood pneumonias (patient group 1) had an expansion of effector memory $ CD8^{+} $ T-cells with the senescent phenotype when compared to HCs. Such changes were not observed in the patient group 2 (four patients, 16, 22, 24, and 33 years old) who were life-long adherents to prophylaxis and experienced few infectious complications. CyTOF analysis of $ CD8^{+} $ T-cells from the 5-year-old patient and older adult HCs showed similar expression patterns of senescence-associated molecules. Conclusions Our findings support that recurrent infections and non-adherence to prophylaxis promote early $ CD8^{+} $ T-cell senescence in CD40L deficiency. Premature senescence may increase malignant susceptibilities and further exacerbate infectious risk in CD40L-deficient patients. |
abstractGer |
Purpose CD40 ligand (CD40L)-deficient patients display increased susceptibilities to infections that can be mitigated with effective prophylactic strategies including immunoglobulin G (IgG) replacement and prophylactic antibiotics. $ CD8^{+} $ T-cell senescence has been described in CD40L deficiency, but it is unclear if this is an intrinsic feature of the disease or secondary to infectious exposures. To address this question, we assessed $ CD8^{+} $ T-cell senescence and its relationship to clinical histories, including prophylaxis adherence and infections, in CD40L-deficient patients. Methods Peripheral $ CD8^{+} $ T-cells from seven CD40L-deficient patients and healthy controls (HCs) were assessed for senescent features using T-cell receptor excision circle (TREC) analysis, flow cytometry, cytometry by time of flight (CyTOF) and in vitro functional determinations including CMV-specific proliferation and cytokine release assays. Results Three patients (5, 28, and 34 years old) who were poorly adherent to immunoglobulin G replacement and Pneumocystis jirovecii pneumonia (PJP) prophylaxis and/or experienced multiple childhood pneumonias (patient group 1) had an expansion of effector memory $ CD8^{+} $ T-cells with the senescent phenotype when compared to HCs. Such changes were not observed in the patient group 2 (four patients, 16, 22, 24, and 33 years old) who were life-long adherents to prophylaxis and experienced few infectious complications. CyTOF analysis of $ CD8^{+} $ T-cells from the 5-year-old patient and older adult HCs showed similar expression patterns of senescence-associated molecules. Conclusions Our findings support that recurrent infections and non-adherence to prophylaxis promote early $ CD8^{+} $ T-cell senescence in CD40L deficiency. Premature senescence may increase malignant susceptibilities and further exacerbate infectious risk in CD40L-deficient patients. |
abstract_unstemmed |
Purpose CD40 ligand (CD40L)-deficient patients display increased susceptibilities to infections that can be mitigated with effective prophylactic strategies including immunoglobulin G (IgG) replacement and prophylactic antibiotics. $ CD8^{+} $ T-cell senescence has been described in CD40L deficiency, but it is unclear if this is an intrinsic feature of the disease or secondary to infectious exposures. To address this question, we assessed $ CD8^{+} $ T-cell senescence and its relationship to clinical histories, including prophylaxis adherence and infections, in CD40L-deficient patients. Methods Peripheral $ CD8^{+} $ T-cells from seven CD40L-deficient patients and healthy controls (HCs) were assessed for senescent features using T-cell receptor excision circle (TREC) analysis, flow cytometry, cytometry by time of flight (CyTOF) and in vitro functional determinations including CMV-specific proliferation and cytokine release assays. Results Three patients (5, 28, and 34 years old) who were poorly adherent to immunoglobulin G replacement and Pneumocystis jirovecii pneumonia (PJP) prophylaxis and/or experienced multiple childhood pneumonias (patient group 1) had an expansion of effector memory $ CD8^{+} $ T-cells with the senescent phenotype when compared to HCs. Such changes were not observed in the patient group 2 (four patients, 16, 22, 24, and 33 years old) who were life-long adherents to prophylaxis and experienced few infectious complications. CyTOF analysis of $ CD8^{+} $ T-cells from the 5-year-old patient and older adult HCs showed similar expression patterns of senescence-associated molecules. Conclusions Our findings support that recurrent infections and non-adherence to prophylaxis promote early $ CD8^{+} $ T-cell senescence in CD40L deficiency. Premature senescence may increase malignant susceptibilities and further exacerbate infectious risk in CD40L-deficient patients. |
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Infectious Complications Predict Premature $ CD8^{+} $ T-cell Senescence in CD40 Ligand-Deficient Patients |
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Catanzaro, Jason Yonkof, Jennifer R. Delmonte, Ottavia Sacco, Keith Shin, Min Sun Reddy, Srikar Whittington, Paula J. Soffer, Gary Mustillo, Peter J. Sullivan, Kathleen E. Notarangelo, Luigi D. Abraham, Roshini S. Romberg, Neil Kang, Insoo |
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score |
7.402135 |